The primary objective of this project is to determine how solute permeability and the activity of various transport systems are affected by constituents of the cell membrane. The experimental approach being used is to alter bacterial membrane composition using nutritional deficiencies and genetic mutations, and then to determine the resultant changes in uptake and retention of amino acids and other solutes. For example, Lactobacillus plantarum and various Escherichia coli mutants in which fatty acid and lipid composition have been altered display concomitant and frequently heterogeneous changes in transport and retention of amino acids. By manipulating the lipid composition in such cells and observing the resultant changes in permeability and transport system activity, we hope to define some of the structural and metabolic requirements of the membrane permeation systems. Experiments of this type also will be carried out with cultured mammalian cells and with bacterial membrane vesicles modified by fusion with liposomes.